Monday, December 3, 2007

2.3.2 ARMD

ARMD or AMD = age-related macular degeneration. This is a much dreaded eye disease in the elderlies in the US.

OK, some commonly thrown around numbers first: 10% of 66-74 and 30% of >75 year-olds will develop AMD, and 80% of which will be in the dry form (and the rest, the wet form). Quite a bit of research has been done on AMD, from risk factors to genetics to therapy. Here, we'll concentrate on prevention and treatment.

First, we need to make a diagnosis. Sometimes, patients are devastated by the diagnosis of AMD as they often associate it, incorrectly, with total blindness.

Usually what alerts the clinicians to AMD is the appearance of multiple drusens in the macular area. A lone one or two, located way out in the periphery, usually does not mean much except maybe an indication of high cholesterol. The image below is the fundus photo of a right eye. To the right, the oval structure is the optic disc, from it, arteries and veins originate and extend to arc above and below the macula.

Drusens are yellowish little round objects (see above, scattering in the macular region) that contain protein and fat, probably byproducts of the immune system. It is still a mystery what causes the production of drusens. They are found between the pigment epithelium and the choroid and seem to choke off the blood supply to the macula. As a result, this retinal area atrophied (this is the dry form). In some cases, new blood vessels are invited in, to re-supply oxygen. These blood vessels upset the integrity of the macular structure and often they leak (which can be assessed with fluorescein angiography)(this is the exudative, or the neovascular, but more commonly known as the wet form). In both cases, the macular function gradually deteriorates and is finally lost. And you now have a central scotoma. A video clip illustrating the evolution of a very dense scotoma is seen below (courtesy of NEI/NIH):

It should be noted that this video compresses years of gradual change into a few seconds. There are measures you can now take immediately upon diagnosis. On the prevention front, some clear evidence is beginning to emerge. In a study concluded in late 2007, the intake of lutein and zeaxanthin seems to reduce the risk of AMD. Foods containing these nutrients include Brussels sprouts, peas, corn, zucchini, broccoli, etc. And dark leafy greens are usually good sources. A daily dose of spinach is highly recommended.

An earlier study already has found a 25% reduction of risk in developing advanced AMD, through intake of vitamin C, vitamin E, vitamin A, and zinc - later modified to vitamins C and E, lutein, and zinc. There are now several OTC versions available. To be prudent, if you have a family history of AMD, it is a good idea to pay more specific attention to nutrition.

On the medical front, the introduction of anti-angiogenics (anti-VGEF monoclonal antibodies) has opened a small albeit important door to the treatment of wet AMD. Lucentis and its far less expensive generic form, Avastin have both been found efficacious in arresting and even limited reversal of AMD. They must be injected directly into the eye, however. Pain? Not too much.

Lucentis, in conjunction with photodynamic therapy (PDT) may even be more efficacious. Only time can tell. PDT is of course based on laser light activation of an intravenously adminstered dye, Visudyne, thereby destroying new blood vessels in the macular area.

All these require multiple treatments and the main goal is really to stablize not to significantly improve the residual vision.

And in the worse case, it is still possible to re-direct the light to retinal areas outside of the damaged macula, and the patient can regain some reading abilities. This is because a different area of the retina, outside of the scotoma, can be called upon to see. We have named these areas PRLs (Preferred Retinal Loci). A special instrument SLO (Scanning Laser Ophthalmoscope) is used to first identify the PRL. Reading materials are projected directly onto the PRL, and each patient’s reading rate is then measured. The results show that the average reading speed of patients with PRL of Area 1 (below the central scotoma) is significantly faster at 72 wpm (words per minute), than Area 2 (away from both the scotoma and the optic disc) at 62 wpm, and Area 3 (between the scotoma and the optic disc) at 31 wpm. In other words, inferior PRL (Area 1), especially that with an initial point of reading located inside the PRL but away from the scotoma, is the most optimal for reading. Based on these findings, by using the SLO to train the patients to use Area 1 for more efficient reading, it can greatly improve the patients’ quality of life.